The liver cytochrome P-450's which are involved in the metabolism of drugs, carcinogens and other xenobiotics can also be induced by some of these same copounds. However, in diseased or damaged livers, cytochrome P-450 levels are low. At the present time, little is known regarding the regulation of the cytochrome P-450's in the normal or diseased liver states. In order to study this problem, I propose to purify the mRNA coding for rabbit liver cytochrome P-450-LM2 (which is inducible by phenobarbital)k, synthesize a radioactive complementary DNA (cDNA), and use the cDNA as a probe to quantitate cytochrome P-450-LM2 mRNA levels in normal liver, during drug induction and during the development of liver damage or disease. If the mRNA cannot be sufficiently purified such that a pure cDNA can be obtained, then a double stranded cDNA (ds cDNA) will be synthesized, inserted into the plasmid pBR322, and cloned using E coli K-12. The plasmid containing the ds cytochrome P-450-LM2 cDNA will be identified by: a) colony hybridization, b) hybrid arrest translation and c) positive translation. The ds cDNA will be recovered, labelled by nick translation, and then used as a probe for the regulation studies. Overall, the study will give valuable insight into the regulation of cytochrome P-450-LM2 synthesis and on the role that the cytochrome P-450's play in the etiology of liver damage or disease.